Aoi Kimishima, Rina Suzuki, Taichi Kamo, Paul Wasuwanich, Hidehito Matsui, Sota Negami, Sota Honma, Yukiko Ujie, Naozumi Kondo, Hideaki Hanaki, Yukihiro Asami
Designed and synthesized catechol-conjugated azithromycin derivatives and evaluated their anti-P. aeruginosa activity due to the bacteria's inherent resistance to many antibiotics. One of the derivatives showed superior antibacterial activity to azithromycin, even against MDR P. aeruginosa clinical isolates. The creation of azithromycin derivatives based on a Trojan horse strategy shows promise in combating Pseudomonas aeruginosa infection.
Due to Pseudomonas aeruginosa (P. aeruginosa)'s inherent resistance to many antibiotics and the increasing incidence of multidrug-resistant (MDR) organisms, P. aeruginosa infection has become a growing global threat to humanity. Azithromycin (AZM) does not have prominent antibacterial activity against P. aeruginosa at a clinically reasonable level because of the bacteria's outer membrane and efflux pump system; however, it does demonstrate other properties, including reduction of inflammation and suppression of P. aeruginosa virulence. With the promising potential of AZM as an anti-P. aeruginosa active compound, we proposed the application of a Trojan horse strategy to the synthesis of AZM derivatives. In this study, we designed and synthesized catechol-conjugated AZM derivatives and evaluated their anti-P. aeruginosa activity. One of the derivatives showed superior antibacterial activity to AZM, even against MDR P. aeruginosa clinical isolates.